This application Abdominal Symptom Phenotype: Pathways to New Biomarkers (ASPPNB) is in response to RFA-OD-09-004, American Recovery and Reinvestment Act for research and infrastructure. This application is responsive to NINR priorities related to discovery of biomarkers and understanding linkages between symptoms and biomarkers, the mechanisms leading to symptoms, and ultimately symptom management. Functional gastrointestinal (GI) disorders (FGIDs), in particular irritable bowel syndrome (IBS) in adults and children, are among the most common and costly health care problems in the US. In adults, IBS disproportionately affects women (10-15% of women in western nations) and adolescent girls. There are well-recognized associations between IBS and other conditions (fibromyalgia, headache) and symptoms (depression, fatigue, insomnia). Therapies are typically prescribed to relieve particular symptoms (drugs such as antispasmodics, analgesics or antidepressants for pain, laxatives, antidiarrheals) or change lifestyle features (e.g., diet, cognitive behavioral therapy, hypnosis, or comprehensive self management2, 3 to modify coping ability). We posit that by understanding better these different expressions of IBS (i.e., better defined patient subgroups) and linking them to newer biomarkers, ultimately greater progress on understanding the etiologies and defining effective treatments can be achieved. Our Specific Aims are to 1) use existing symptom diary data on 400 women with IBS from two studies to define clusters of women with differing symptoms. A similar approach will be taken using diary data from 100 girls with IBS. 2) Perform proteomic analyses of urine samples from the women and girls in Aim 1 and identify potential biomarkers, namely proteins whose levels differ between IBS and Control groups. 3) Advances in high throughput genomics and proteomics have increased the potential for new biomarkers including urine proteomics. We will recruit 20 women and 20 girls with IBS and 40 Controls (20 women, 20 girls). Collect diary data, urine samples for proteomics, serum for lymphocyte activation, cytokine expression and perform DNIC and video capsule endoscopy procedures. The goals of this application will be accomplished by developing infrastructure (equipment and collaborations), partnerships with industry and resources necessary to collect preliminary data for larger mechanistic and intervention studies. PUBLIC HEALTH RELEVANCE: Functional gastrointestinal disorders, in particular functional abdominal pain (FAP) in children and adults and irritable bowel syndrome (IBS) in adults, are among the most common and costly health care problems in the U.S. These functional pain conditions disproportionately affect women (10-15% in industrialized nations) and adolescent girls, and likely have multiple causes and symptom profiles. Until we have some way of identifying subgroups, progress on understanding etiology will be difficult to achieve. The goal of this proposed interdisciplinary study is to use existing symptom data and urine samples from 400 adults and 100 children with IBS to define clusters of patients with distinct symptom profiles and then test whether urinary proteomics can identify biomarkers which distinguish these symptom subtypes from each other and from healthy controls. New biomarkers (video capsule endoscopy, lymphocyte activation/cytokine diffuse noxious inhibitory control testing) will be used with newly recruited IBS and control subjects.